Tubulointerstitial Macrophage Accumulation is Regulated by Sequentially Expressed Osteopontin and Macrophage Colony-Stimulating Factor: Implication for the Role of Atorvastatin

Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1(+) cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1(+) cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1(+) cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1(+) cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF

Arterial Stiffness as a Predictor of the Index of Atherosclerotic Cardiovascular Disease in Hypertensive Patients

Objective: The aim of this study was to evaluate the predictive value of carotid-femoral pulse wave velocity (cfPWV) and cardiovascular disease in the hypertensive population in China and to determine the specific cfPWV cut-off value for assessing future cardiovascular disease (CVD) risk. Methods: This cross-sectional study included 630 hospital patients with primary hypertension and multiple cardiovascular risk factors or complications involving damage to clinical target organs. The study was conducted between July 2007 and October 2008. Atherosclerotic cardiovascular disease (ASCVD) risk calculations were computed according to criteria presented by the American College of Cardiology and the American Heart Association. Patients were stratified by a predefined risk threshold of 10% and divided into two groups: ASCVD ≥ 10% or ASCVD p p p p p < 0.001, respectively); the optimal critical value of cfPWV and aortic SBP was 12.45 m/s (sensitivity 63.2%, specificity 77.8%) and 124.5 mmHg (sensitivity 63.9%, specificity 65.3%). Conclusions: cfPWV is significantly correlated with the risk of ASCVD. The best cut-off value of cfPWV for assessing future CVD risk in the hypertensive population in China is 12.45 m/s

Central aortic pressure improves prediction of cardiovascular events compared to peripheral blood pressure in short-term follow-up of a hypertensive cohort

Objective: The aim of this study was to assess indices of a comprehensive panel of central aortic pressure and arterial stiffness for prediction of cardiovascular events in a hypertensive cohort. Methods: Noninvasive measurements of central aortic blood pressure, brachial pressure, wave reflection augmentation index, pressure amplification, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) were obtained in 675 hypertensive patients (age 61 ± 9 years, 425 males) for a mean follow-up period 25 ± 4 months. The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD. Results: After adjusting for confounding factors, central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events (CV) compared to peripheral pressure indices (pSBP, pPP) at age >60 years (cSBP: HR = 1.18, pSBP: HR = 1.17, p = 0.034; cPP: HR = 1.28, pPP: HR = 1.2, p = 0.019). Each SD increase in IMT and in central augmented pressure (cAP) entailed a 1.4 times higher risk of increased total events in elderly patients (age >60 years). For males, each SD increase in cAP was associated with 1.36 times higher risk of increased total events. For females, each SD increase in cAIx and cAP was associated with 0.4 and 0.5 times lower risk of increased total and major CV, respectively. This sex difference is most likely due to lack of age-related increase of cAIx in females after age >60 years compared to males. Conclusions: Central pressure improved prediction of CVD compared to peripheral pressure during a relatively short-term follow up of approximately 2 years at age >60 years